Diabetes is a general term for disorders in man having excessive urine excretion as in diabetes mellitus and diabetes insipidus. Diabetes mellitus is a metabolic disorder in which the ability to utilize glucose is partly or completely lost.
Since the discovery of insulin in the 1920's, continuous strides have been made to improve the treatment of diabetes mellitus. To help avoid extreme glycaemia levels, diabetic patients often practice multiple injection therapy, whereby insulin is administered with each meal. Many diabetic patients are treated with multiple daily insulin injections in a regimen comprising one or two daily injections of a protracted insulin composition to cover the basal requirement, supplemented by bolus injections of a rapid acting insulin to cover the meal-related requirements.
Insulin compositions having a protracted profile of action are well known in the art. Thus, one main type of such insulin compositions comprises injectable aqueous suspensions of insulin crystals or amorphous insulin. Typically, the insulin in these compositions is provided in the form of protamine insulin, zinc insulin or protamine zinc insulin.
When human or animal insulin is brought to form higher associated forms, e.g. in the presence of Zn2+-ions, precipitation in the form of crystals or amorphous product is the result; see for example pages 20–27 in Jens Brange (editor), Galenics of Insulin, Springer Verlag (1987). Thus, at pH 7, addition of 6 Zn2+ ions per insulin hexamer to a solution of porcine insulin will lead to an almost complete precipitation of the insulin.